Various neurological disorders disrupt the communication matrix between supraspinal centers and spinal circuits, which leads to a range of motor disabilities.
For example, a neuromotor impairment can be consequent to a spinal cord injury (SCI), an ischemic injury resulting from a stroke, or a neurodegenerative disease, such as Parkinson's disease.
In particular, after spinal cord lesion, either cervical or thoracic, motorpools do not receive inputs from the supraspinal structures despite spinal motor circuits remaining functional.
Neuromodulation strategies provide access to surviving circuits and pathways to alleviate these deficits (1, 2). In particular, electrical and chemical neuromodulation of the lumbar spinal cord has mediated significant improvement of lower-limb motor control in animal models (3-7) and humans (6, 8-11) with SCI.
Computer simulations (12-14) and experimental studies (7, 15-17) have provided evidence that electrical neuromodulation applied to the dorsal aspect of lumbar segments primarily engages proprioceptive feedback circuits recruited by the stimulation of dorsal roots fibers. The prevailing view is that the recruitment of these neural pathways activates central-pattern generating networks (9, 18) and raises the excitability of spinal circuits to a level that enables sensory information to become a source of motor control (19).
However, movement production is orchestrated by the coordinated activation of motorpools along the spinal cord that are activated with specific and precise timing by the central nervous system.
In particular, the production of limb movements involves the activation of spatially distributed motoneurons (21, 22) following precise temporal sequences (23, 24) that are continuously adjusted through sensory feedback (25).
Therefore, effective therapies should aim at the precise activation of spinal circuits in space and time.
This framework enacted two fundamental limitations in the clinical application of electrical neuromodulation therapies. First, the spatial location of stimulation remains confined to single spinal cord regions that are selected using empirical mapping experiments (9, 20). Second, the temporal structure of stimulation protocols is restricted to non-modulated patterns that remain constant during motor execution, regardless of the current state of lower-limb movements (8, 9, 15).
Therefore, the design of spatiotemporal neuromodulation therapies to facilitate motor control in clinical settings relies on a series of non-trivial methodological developments. First, the design of spatially selective implants that can specifically target motor circuits via the recruitment of dorsal roots fibers. Second, the design of time specific stimulation patterns that target in real-time motoneurons located in spatially restricted regions.
Current stimulation protocols and systems do not attempt to reproduce these spatiotemporal patterns of motoneuron activation to facilitate movement. Indeed, they remain unspecific, restricted to single regions and delivered continuously.
Therefore, there is the need of a system integrating spatial selectivity and temporal structure to improve stimulation efficacy and thus motor control.
In particular, there is still the need of a system for stimulating specific spinal roots with a precise temporal resolution so that different, specific motor-pools can be activated during different gait phases.
Computational models and experimental works (12, 13, 15, 16) have shown that epidural electrical stimulation (EES) of the lumbar spinal cord mainly recruits large myelinated afferents fibers located in the dorsal roots. Efferent fibers can also be recruited in particular at the caudal/sacral level. After spinal cord injury, during non-specific EES, muscle activity is composed of a burst of mono-synaptic and poly-synaptic components produced by the recruitment of dorsal root afferents often termed spinal reflexes (12). This muscle activity is modulated (7, 12) and gated by the spinal circuitry to build locomotor patterns and modulate kinematic variables (7).
These results have been obtained in experimental animals and humans with severe motor deficits (9, 19).
However, incomplete lesions can also result in the impossibility of movement despite remaining motor control abilities.
Moreover clinical lesions differ from case to case due to the variability in the nature, location and severity of the lesion. Each patient shows specific motor deficits that have to be selectively targeted to regain motor functions.
In order to selectively correct these deficits, the effects of EES should be focused on the impaired joint/functions. Joint/function specific EES would thus require the selective stimulation of a subset of dorsal roots in order to trigger joint/function specific spinal reflexes.
In view of the above, spinal dorsal roots should be selectively targeted in order to promote specific limb movements thus allowing restoration of motion.
Furthermore, in order to ensure a sufficient level of specificity, single rootlets should be targeted, granting in this way the access to motorpools located at specific segments thus improving muscle specificity.
The use of multi-electrode array devices for epidural stimulation in the rehabilitation of spinal cord injuries is known (33).
However, they are not able to achieve a high specificity of stimulation, in particular of specifically selected dorsal roots and muscles.
Indeed, state of the art multi-electrode arrays are designed to activate specific spinal segments based on the close proximity between the electrode and the said stimulated segment. Accordingly, the electrodes are placed on the dorsal surface of the cord, at regular intervals along the rostro-caudal extent based on the underlying longitudinal segmental structure. This design was mainly driven from pain applications, where the dorsal column fibers are targeted. Indeed, current clinical devices have been designed to specifically target myelinated fibers contained in dorsal columns to suppress neuropathic pain according to the gate theory (26).
In view of the above, there is still the need of a system for a selective spatial targeting and stimulation of specific spinal roots, in particular spinal dorsal roots.
As mentioned above, devices for spinal neurostimulation are known in the art of pain treatment.
US20070179579 discloses a method for neurostimulation to treat multiple pain locations. In the method, a multi-column, multi-row paddle lead is used to stimulate dorsal column fibers to act on pain locations. Electrode combinations are determined to address the pain and an implantable pulse generator (IPG) is used to deliver pulses according to said electrode combinations.
US2010280570 discloses an apparatus for stimulating the spinal cord for pain treatment, wherein the spinal cord contact surfaces are arranged in a plurality of rows, wherein the rows extend in a transverse direction to the extent of the spinal cord and adjacent rows of stimulation contact surfaces are arranged at a distance from one another in the direction of the extent of the spinal cord.
U.S. Pat. No. 5,643,330 discloses an apparatus for EES using a multi-channel pulse generator and an electrode transverse and facing the spinal cord.
US20070168008 and US2006122678 disclose a transverse tripole stimulation in which electrodes can be arranged in a direction transverse relative to the spinal cord.
US2007179579 discloses a paddle lead, which can be implanted in a patient for pain treatment.
US2014088674 discloses targeting spinal roots (dorsal and ventral) and motor nerve rootlets for pain treatment.
The above disclosed devices are used for pain treatment. This is a completely different field from the one of motor disorders, which is the field of the present disclosure. Indeed, in pain treatment, accidental movements are a side effect of the treatment and therefore should be carefully avoided. Devices are designed and used in order to target the spinal regions involved in pain and to avoid targeting of spinal regions involved in locomotion. On the contrary, the aim of the present application is the achievement of locomotion and in particular the specific target of the spinal structures involved in movement production.
It has now been found a system for electrical neuromodulation therapies capable of integrating spatial selectivity and temporal structure matching the natural dynamics of motoneuron activation and improve stimulation efficacy, enhancing the quality and vigor of lower-limb movements after SCI.
In particular, it has been found a stimulation system able to spatially and temporally specifically target the spinal dorsal roots in order to achieve a more selective activation of the desired motor circuits and therefore a more efficient movement production.
It has further been found that a multi-electrode array tailored to the dorsal roots anatomy together with multipolar stimulation allows modulating the shape of the stimulating field thus increasing stimulation specificity.